Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to calicheamicin, a cytotoxic antitumor antibiotic. GO is indicated for the treatment of newly-diagnosed or relapsed/refractory CD33-positive acute myeloid leukemia (AML).
Phase | Patient Population | Median Age of Patients in Years (Range) | Evaluable Patients | GO Dosing | Treatment Plan | Outcomes | Ref. |
---|---|---|---|---|---|---|---|
I | Relapsed/refractory AML patients | 54 (24–73) | 40 | Escalating doses, 0.25 to 9 mg/m2 | Single arm trial, GO administered as single agent | ORR: 8/40 patients (20%) | Sievers 1999 [3] |
II | AML patients in first relapse | 61 (22–84) | 142 | 9 mg/m2, 2 doses recommended (max. 3 doses), with at least 14 days between 2 doses | Single arm trial, GO administered as single agent | ORR: 42/142 patients (30%), CR rate: 16%, CRp rate: 13% | Sievers 2001 [4] |
II | De novo AML in first relapse | 64 (22–80) | 57 | Fractionated doses: 3 mg/m2 on days 1, 4 and 7 of the first course | Single arm trial, GO administered as single agent in induction, followed by cytarabine-based consolidation | ORR: 19/57 (33%), CR rate: 15/57 (26%), CRp: 4/57 (7%) | Taksin 2007 [5] |
I/II | De novo AML in first relapse | 60 (40–70) | 20 | Fractionated doses: 3 mg/m2 on days 1, 4 and 7 of the first course | Single arm trial, GO combined with DA (DA dosing finding) | ORR: 13/20 patients (65%), CR rate: 11/20 patients (55%), CRp rate: 2/20 patients (10%) | Farhat 2012 [6] |
III | De novo/secondary AML | 50 (15–71) | 1113 | 3 mg/m2 on day 1 of course 1 +/− on day 1 of the course 3 | Randomization at induction and at consolidation. Induction regimen (DA or ADE or FLAG-Ida) +/− GO. Consolidation regimen (MACE or MidAC or high-dose cytarabine) +/− GO | GO- vs. no GO-arm: CR, 82% vs. 83%, OR: 1.04, 95% CI: 0.76–1.42, p = 0.8; 5-year OS, 43% vs. 41%, HR: 0.92, 95% CI: 0.79–1.08, p = 0.3; 5-year RFS: 39% vs. 35%, HR: 0.87, 95% CI: 0.73–1.02, p = 0.09 | Burnett 2011 [7] |
III | De novo AML | 47 (18–60) | 595 | 6 mg/m2 on day 4; additional 3 doses of GO, 5 mg/m2 for patients in CR after consolidation | Randomized trial, GO plus modified DA (daunorubicin, 45 mg/m2/d, day 1 to day 3; cytarabine, 100 mg/m2/d, day 1 to day 7) vs. standard DA (daunorubicin, 60 mg/m2/d, day 1 to day 3; cytarabine, 100 mg/m2/d, day 1 to day 7) | DA + GO vs. DA alone: ORR: 76% vs. 74%, p = 0.36; CR rate: 69% vs. 70%, p = 0.59; 5-year RFS: 43% vs. 42%, p = 0.40; 5-year OS: 46% vs. 50%, p = 0.85 | Petersdorf 2013 [8] |
III | De novo/secondary AML and high-risk MDS | 67 (51–84) | 1115 | 3 mg/m2 on day 1 of the first course | Randomized trial: DA or daunorubicin/clofarabine +/− GO | GO- vs. no GO-arm: ORR: 70% vs. 68%, OR: 0.88, 95% CI: 0.68–1.13, p = 0.3; 3-year OS: 25% vs. 20%; HR: 0.87, 95% CI: 0.76–1.00, p = 0.05; 3-year RFS: 21% vs. 16%, HR: 0.84, 95%CI: 0.71–0.99, p = 0.04 | Burnett 2012 [9] |
III | De novo AML patients with intermediate cytogenetic risk | 50 (18–60) | 238 | 6 mg/m2 on day 4 of the induction and on day 4 of the first consolidation course | Randomized trial: intensive induction regimen (DA) +/− GO, consolidation (MidAC) +/− GO, +/− HSCT | GO- vs. no-GO-arm: CR rate: 91.6% vs. 86.5%, p = NS; 3-year OS: 53% vs. 46%, p = NS; 3-year EFS: 51% vs. 33%, p = NS. In non HSCT recipients, GO vs. no GO-arm: 3-year EFS: 53.7% vs. 27%, p = 0.0308 | Delaunay 2011 [10] |
III | De novo AML | 62 (50–70) | 271 | 3 mg/m2 on days 1, 4, and 7 of induction and on day 1 of each of the subsequent two consolidation courses | Randomized trial: DA +/− GO | GO- vs. no-GO-arm: ORR: 81.5% vs. 73.5% (p = 0.15) (CR: 70.4% vs. 69.9%; CRp:11.1% vs. 3.7%); median EFS: 13.6 months vs. 8.5 months, HR: 0.66, 95% CI: 0.49–0.89, p = 0.006; median OS: 27.5 months vs. 21.8 months, HR: 0.81, 95% CI: 0.60–1.09, p = 0.16 | Castaigne 2012, Lambert 2019 [11][12] |
III | De novo or secondary AML and high-risk MDS | 50 (0–81) | 788 | 3 mg/m2 vs. 6 mg/m2 on day 1 of induction | Randomized trial: GO 3 vs. 6 mg/m2 + combined with ADE vs. DA | GO 3 mg/m2 vs. 6 mg/m2: ORR: 89% vs. 86%, HR: 1.34, 95%CI:0.88–2.04, p = 0.17; (CR rate 82% vs. 76%, OR: 1.46, 95%CI: 1.04–2.06, p = 0.03); 4-year OS: 50% vs. 47%, HR: 1.10, 95% CI: 0.90–1.34, p = 0.3; 4-year RFS: 44% vs. 38%, HR: 1.11, 95% CI: 0.91–1.35, p = 0.3 | Burnett 2016 [13] |
III | De novo/secondary AML | 67 (60–75) | 472 | 3 mg/m2 for 2 doses, on days 1 and 15 of induction, 3 mg/m2 on the first day of consolidation | Randomized trial: intensive chemotherapy (MICE induction) +/− GO | GO vs. no-GO-arm: ORR: 45% vs. 49%; OR: 0.86, 95% CI, 0.6–1.23, p = 0.46; OS: HR: 1.20, 95% CI: 0.99–1.45, p = 0.07; RFS: HR: 1.08, 95% CI: 0.81–1.44, p = 0.61 | Amadori 2013 [14] |
III | De novo/secondary AML unfit for intensive chemotherapy | 77 (62–88) | 237 | 6 mg/m2 on day 1 and 3 mg/m2 on day 8, +/−2 mg/m2/month for up to 8 doses | Randomized trial: GO alone vs. BSC | GO- vs. BSC-arm: median OS: 4.9 months vs. 3.6 months, HR: 0.69, 95% CI: 0.53–0.90, p = 0.005 | Amadori 2016 [15] |
I | Relapsed/refractory AML patients | 12 (1–16) | 29 | Escalating doses, 6 to 9 mg/m2 | Single arm trial, GO administered as single agent | ORR: 8/29 patients (28%); CR rate: 14%; CRp rate: 14%) | Arceci et al. 2005 [16] |
II | Refractory de novo AML or newly diagnosed secondary AML | 11.5 (0.8–19.8) | 45 | 2 to 3 mg/m2 | Non randomized multi-arm trial, GO + cytarabine + mitoxantrone (arm A) vs. GO+ cytarabine+ L-asparaginase (arm B) | Arm A vs. arm B: ORR: 55% vs. 40%, p = NS; 1-year EFS: 55% vs. 21.8%, p = NS; 1-year OS: 64.6% vs. 45.0% p = NS | Aplenc 2008 [17] |
II | Newly diagnosed de novo AML | 9.5 (0.07–21.6) | 340 | 3 mg/m2 on day 6 of course 1 and day 7 of course 4 | Single arm trial, GO combined with intensive chemotherapy | CR rate: 83.1%; 3-year OS: 66%; 3-year EFS: 53% | Cooper 2012 [18] |
III | Newly diagnosed de novo AML | 9.7 (0–29) | 1022 | 3 mg/m2 on day 6 of induction course 1, and on day 7 of intensification course 2 | Randomized trial, GO +/− standard chemotherapy | GO- vs. no-GO arm: CR rate: 88.3% vs. 85.1, p = 0.15; 3-year EFS: 53.1% vs. 46.9%, HR: 0.83, 95% CI: 0.70–0.99, p = 0.04; 3-year OS: 69.4% vs. 65.4%; HR: 0.91, 95% CI: 0.74–1.13, p = 0.39 | Gamis 2014 [19] |
This entry is adapted from the peer-reviewed paper 10.3390/ijms21165626